Faculty Collaboration Database

Heat shock inhibits cytokine-induced nitric oxide synthase expression by rat and human islets. Endocrinology 1998 Dec;139(12):5050-7

Date

12/01/1998

Pubmed ID

9832444

DOI

10.1210/endo.139.12.6366

Scopus ID

2-s2.0-0031757110 (requires institutional sign-in at Scopus site)   103 Citations

Abstract

In this study the effects of heat shock on interleukin-1beta (IL-1)-induced inhibition of islet metabolic function were examined. Treatment of rat islets for 18 h with IL-1 results in a potent inhibition of glucose-stimulated insulin secretion. The inhibitory effects of IL-1 on insulin secretion are completely prevented if islets are pretreated for 60 min at 42 C before cytokine stimulation. Heat shock also prevents IL-1-induced inhibition of insulinoma RINm5F cell mitochondrial aconitase activity. The protective effects of heat shock on islet metabolic function are associated with the inhibition of IL-1-stimulated inducible nitric oxide synthase (iNOS or NOS II) expression. Islets heat shocked for 60 min at 42 C fail to express iNOS (messenger RNA or protein) or produce nitrite in response to IL-1. IL-1-induced iNOS expression by rat islets requires activation of the transcriptional regulator nuclear factor kappaB (NF-kappaB). Heat shock prevents IL-1-induced NF-kappaB nuclear localization by inhibiting inhibitory protein kappaB (IkappaB) degradation in rat islets. Similar to rat islets, heat shock (stimulated by 90 min incubation at 42 C) prevents IL-1 + interferon gamma-induced iNOS expression and NF-kappaB nuclear localization in human islets. IL-1 also stimulates heat-shock protein 70 (hsp 70) expression by rat islets, and hsp 70 expression is dependent on islet production of nitric oxide. Last, evidence is presented that implicates nitric oxide as a stimulus for the expression of proteins that participate in islet recovery from nitric oxide-mediated damage. These studies indicate that heat shock prevents cytokine-induced islet damage by inhibiting iNOS expression, and suggest that nitric oxide is one effector molecule that stimulates the expression of factors involved in beta-cell recovery from nitric oxide-mediated damage.

Author List

Scarim AL, Heitmeier MR, Corbett JA

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aconitate Hydratase
Animals
Cytokines
DNA-Binding Proteins
HSP70 Heat-Shock Proteins
Hot Temperature
Humans
Hydrazines
I-kappa B Proteins
Insulin
Interleukin-1
Islets of Langerhans
Male
Mitochondria
NF-kappa B
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrogen Oxides
RNA, Messenger
Rats
Rats, Sprague-Dawley
Shock